Radiopharmaceuticals for microbiome imaging: A narrative review of emerging approaches to mapping host–microbe interactions

The human microbiome has immense effects on immunity, metabolism, and therapeutic response, but non-invasive in vivo visualization is underdeveloped. Radiopharmaceuticals, traditionally applied in oncology and cardiology, are now emerging as a novel method for mapping host-microbe interactions. This review is a critical analysis of current advances, issues and future prospects in microbiome-targeted nuclear imaging. The preclinical and translational literature was thoroughly analyzed and revealed the principles of radiotracer design, special microbial targets (metabolites, enzymes, transporters, quorum signals), and imaging platforms like Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), PET/CT (Computed Tomography), PET/MRI (Magnetic Resonance Imaging). Case studies of infection, dysbiosis, inflammatory bowel disease and immuno-oncology were reviewed. We summarize a radiopharmaceutical toolbox comprising metabolism-based probes ([ˆ 18 F]-FDS, [ˆ11C]-acetate), siderophore tracers, and radiolabeled antibiotics/peptides. Preclinical data demonstrate the capacity to quantify microbial fluxes, image metabolites such as Short-Chain Fatty Acid (SCFAs) and bile acids, and map organ-specific colonization. The initial human trials demonstrate promise, but lack specificity and have pharmacokinetic issues, as well as regulatory challenges. Radiopharmaceuticals provide a paradigm shift between the microbial detection and functional probing, which provides real-time information on the host–microbe cross-talk. Combination with AI, hybrid imaging, and synthetic biology can increase the speed of translation and precision tracers and theranostic approaches will provide personalized microbiome-directed therapies. The field of nuclear microbiomics is therefore a pioneer in precision medicine.